Hydroxyphenyl-cinnamic nitriles and process



Patented Mar. 18, 1952 HYDROXYPHENYL-CINNAMIC NITRILES AND PROCESS;

Hans Heneoka, Wuppertal-Elberfeld, Germany, assignor to SchenleyLaboratories, Inc., New York, N. Y., a corporation of Delaware NoDrawing. Application November 17, 1949, Se-

rial No. 128,015. In Germany October 5, 1948 9 Claims. 1

This invention relates to a novel class of compounds, thep-hydroxyphenyl-cinnamic acid nitriles.

I have found that B-hydroxyphenyl-cinnamic acid nitriles or theirnuclear substitution products can readily be obtained in a good yield byreacting a beta (methoxymethyloxy phenyl) beta-phenyl-hydracrylic acidnitrileobtainable by condensation of the methoxymethylether of ahydroxybenzophenone with acetonitrile or its mono-substitutionproducts-with acids in the presence of a formaldehyde binding agent. In

an unexpected manner saponification of the methoxy-methyl ether groupand simultaneous dehydration occurs, ,B-hydroxyphenyl-cinnamic acidnitrile being formed. The formaldehyde set free by the saponification ofthe methoxy-methyloxy, group can be chemically reacted with theformaldehyde-binding agent, for instance, phenol or sulfurylamide, thusfacilitating completion of the reaction by removal, in effect, of thisbyproduct. A small quantity of dilute mineral acid is preferably used asan acid catalyst while the preferred solvent is glacial acetic acid.

The new process is applicable to ethers of o-hydroxybenzophenone, aswell as to others of mor p-hydroxybenzophenone. Furthermore, the benzenenuclei of the benzophenone may be substituted by alkyl radicals orhalogen atoms. In these cases, the correspondingly substituted ethers offl-hydroxy-phenyl-cinnamic acid nitriles can easily be produced.

The product obtained by this process, beta-hydroxyphenyl-cinnamic acidnitril, is an important intermediate for the production of anaestheticshaving an activity resembling that of morphine.

The present invention is further illustrated by the following examples:

. Example 1 About 100 grams of beta-(o-methoxymethyloxy-phenyl) -betaphenyl hydracrylic acid nitrile, having a melting point of 123 0., whichmay be obtained by condensation of o-methoxymethyloxy-benzophenone withacetonitrile in an ethereal solution in the presence of sodium amide,are dissolved in a mixture of 500 grams of phenol and 500 cos. ofglacial acetic acid and reacted with 20 cos. of 20 per cent aqueoussulfuric acid at room temperature. After standing for hours the3-o-hydroxyphenyl-cinnamic acid nitrile formed is precipitated incrystals by diluting with three liters of water. By recrystallizing froma mixture of ether and gasoline or from 50 2 per cent acetic acid fine,bright needles are obtained. These needles have a melting point of155-157" C. and are easily soluble in dilute caustic soda solution withlight yellow coloration. The yield amounts to -70 per cent of thetheoretical.

Example 2 Instead of phenol used as a formaldehydeacceptor in Example 1,sulfurylamide may be advantageously employed.

A solution of B-o-methoxymethyloxphenyl-5- phenylhydracrylonitrile and20 g. of sulfurylamide are left to stand for 15 hours in 1500 ccs.glacial acetic acid to which 40 ccs. of 20 per cent aqueous sulfuricacid have been added. On gradual addition of 2500 cos. of waterfl-o-hydroxy-phenyl-cinnamic acid nitrile precipitates in fine crystalsof a high degree of purity and in good yield.

In an analogous manner the following derivatives are obtained:

1. 5-o-Hydroxy-p-tolyl-cinnamic nitrile of the melting point 126-12'7 C.from p-(o-methoxymethyloxy p tolyl) p phenylhydracrylonitrile (meltingpoint -82" C.)

2. B o Hydroxy p tolyl p chloro cinnamic nitrile of the melting point148-150" C. from B (o methoxymethyloxy p tolyl ,8 pchlorophenylhydracrylonitrile (melting point 107-108 C.).

3. 8 o Hydroxy p tolyl p methylcinnamic nitrile of the melting point Ml- C. from ,8 (o methoxymethyloxy p tolyl) ,8- p-tolylhydracrylonitrile(melting point 144- 145 0.).

I claim:

1. As new compounds B-hydroxyphenyl-cinnamic nitriles of the groupconsisting of betaortho hydroxyphenyl cinnamic nitrile,betaortho-hydroxy-para-tolyl-cinnamic nitrile and beta ortho hydroxypara tolyl paraprime-methyl-cinnamic nitrile.

2. As a new compound fi-o-hydroxyphenylcinnamic nitrile.

3. As a new compound ,B-o-hydroxy-p-tolylcinnamic nitrile.

4. As a new compound fl-o-hydroXy-p-tolylp-methyl-cinnamic nitrile.

5. A process of producing fi-hydroxyphenylcinnamic nitriles whichcomprises reacting a 18 methoxymethyloxy phenyl beta phenylhydracrylicnitrile with a dilute aqueous solution of a common mineral acid andwhile dissolved in a water-miscible, acidic, liquid organic s01- ventmedium, under conditions favoring hydrolysis, whereby themethoxymethyloxy substituent is converted to a hydroxyl substituent.

6. A process of producing B-hydroxyphenylcinnamic nitriles whichcomprises reacting a B methoxymethyloxyphenyl p? phenylhydracrylicnitrile with dilute sulfuric acid under conditions favoring hydrolysisof the methoxymethyloxy substituent to a hydroxyl substituent, inglacial acetic solvent.

7. A process of producing fi-hydroxyphenylcinnamic nitriles whichcomprises reacting a B methoxymethyloxyphenyl p phenylhydracrylicnitrile with dilute sulfuric acid under conditions favoring hydrolysisof the methoxymethyloxy substituent to a hydroxyl substituent, inglacial acetic solvent in the presence of a compound capable of bindingformaldehyde.

8. A process of producing fl-hydroxyphenylcinnamic nitriles whichcomprises reacting a 2 4 5 methoxy methyl oxyphenyl fl phenylhydracrylicnitrile with sulfuric acid in glacial acetic acid in the presence ofphenol.

9. A process of producing p-hydroxyphenylcinnamic nitriles whichcomprises reacting a 5 methoxy methyl oxyphenyl p phenylhydracrylicnitrile with sulfuric acid in glacial acetic acid in the presence ofsulfurylamide.

HANS HENECKA.

REFERENCES CITED The following references are of record in the file ofthis patent:

Borsche et al., Beilstein (Handbuch, 4th ed), vol. 10, p. 357 (1927).

Stoermer, Ber. Deut. Chem, vol. 44, pp. 662- 663 (1911).

1. AS NEW COMPOUNDS B-HYDROXYPHENYL-CINNAMIC NITRILES OF THE GROUPCONSISTING OF BETAORTHO - HYDROXYPHENYL - CINNAMIC NITRILE,BETAORTHO-HYDROXY-PARA-TOTYL-CINNAMIC NITRILE AND BETA - ORTHO -HYDROXY - PARA - TOLYL - PARAPRIME-METHYL-CINNAMIC NITRILE.
 5. A PROCESSOF PRODUCING B-HYDROXYPHENYLCINNAMIC NITRILES WHICH COMPRISES REACTING AB - METHOXYMETHYLOXY - PHENYL - BETA - PHENYLHYDRACRYLIC NITRILE WITH ADILUTE AQUEOUS SOLUTION OF A COMMON MINERAL ACID AND WHILEDISSOLVEDSOLIN A WATER-MISCIBLEE, ACIDIC, LIQUID ORGANIC SOLVENT MEDIUM,UNDER CONDITIONS FAVORING HY-DROLYSIS, WHEREBY THE METHOXYMETHYLOXYSUBSTITUENT IS CONVERTED TO A HYDROXYL SUBSTITUENT.